Role of adipose tissue in free fatty acid metabolism in hemorrhagic hypotension and shock. This study was designed to observe the effects of hemmorrhage on the mobilization of free fatty acids from adipose tissue under a variety of experimental conditions. Experiments were conducted in fasting rabbits and dogs. A significant fall in arterial plasma free fatty acids was observed in rabbits following hemorrhage of 4 ml every 2 min and after inducing acute hemmorrhaged to a mean arterial blood pressure of 40 mm mercury. Adipose-tissue free fatty acids and arterial-plasma free fatty acids were simulatneously measured before and after hemorrhagic hypotension until death. Afterial free fatty acids fell significantly following hemorrhage, while the concentration of adipose-tissue free fatty acids rose significantly. In the next series of experiiments, dogs were pretreated with an alpha-receptor blocking agent phenoxybenzamine and acutely hemorrhaged. The results showed a significant rise in arterial free fatty acids concentration and an insignificant increase in adipose-tissue free fatty acids. These results suggest that hypoperfusion of adipose tissue plays an important role in the decreased supply of a major body fuel following hemorrhagic hypotension. The results are compatible with the view that metabolic fuel failure may be an important factor in the development of the complications of acute hemorrhage and suggest the concept that adipose tissue may be an important target organ in hemorrhagic shock.


Reduction of hospital mortality from acute myocardial infarction by anticoagulant therapy. A nationwide study of all 2330 patients hospitalized for a first definite acute myocardial infarction in Israel during a one-year period revealed a significantly lower 21-day mortality rate of patients treated by anticoagulants: 8.3 versus 27.3 per cent in those not receiving such therapy (p less than 0.0001). Out of the 22 hospitals studied, the effect was present in 18, absent in two, and not assessable in two. There was a highly significant inverse correlation between the proportion of patients receiving anticoagulant therapy in each hospital and the total 21-day mortality from infarction in that institution (r equals 0.57; less than 0.01). The superior survival of patients on anticoagulant therapy did not seem related to differences in age, sex, disease severity, site of infarction, diagnostic criteria or type of hospital. Despite the obvious limitations of retrospective studies the data justify a re-evaluation of the approach to the problem by further investigative effort.


Retrospective evidence favoring use of anticoagulants for myocardial infarctions. During a state-wide retrospective study of myocardial infarction discharges from Maryland hospitals from July, 1966, through June, 1967, the relation of in-hospital case fatality rates to use of anticoagulants was examined in 1,156 patients. In patients who did not receive anticoagulants, the rate was 2.5 times that of those who did (p less than 0.0001). A large difference in case fatality rates between the anticoagulant and no-anticoagulant groups persisted when the data were analyzed by demographic and medical-care variables. When patients were classified according to clinical characteristics relating to prognosis, including arrhythmia, congestive heart failure and shock, the difference between the groups were also demonstrated. Although such a retrospective study cannot demonstrate conclusively the value of anticoagulant therapy, the data are sufficiently suggestive of a beneficial effect to warrant reopening the anticoagulant question.


Reserpine and breast cancer in a retirement community. In an attempt to confirm three reports suggesting a causal link between rauwolfia antihypertensive drugs and female breast carcinoma, all cases of such cancer appearing among the residents of an affluent retirement community were compared with controls chosen from a roster of all women in the same community. Most residents use a single care facility, and patterns of hypertension diagnosis, rauwolfia and other drug use, and medical-care-system patronage were abstracted from medical records. The prevalence of recorded rauwolfia use among the controls were 20 per cent, and that of other drug use was correspondingly high. The risk ratio for rauwolfia use was estimated to be 1.2 (95 per cent confidence interval, 0.7 to 2.2). Risk ratios between 1.0 and 2.0 were also found for other drug use and for measures of care-system patronage. These results do not support the hypothesis that reserpine causes breast cancer.


Medical malpractice.

Medical malpractice. Medical liability insurance is in a state of emergency brough on by escalating premiums or withdrawal of insurance companies from the market. Solutions, supported by legislation, must be sought for the sake of both patient and physician. As a temporary method of correction joint underwriting associations appear to be the most practical suggestion. Long-range changes should include the establishment of powerful malpractice arbitration boards whose conclusions and evidence would be submitted in case of further appeal, the delegation of more power to the medical profession to enforce standards, shortening of the period specified in the statutes of limitation, limitations on contingency fees, and elimination of the applicability of such legal doctrines as ad damnum clauses and res ipsa loquitur.


Recurrent ventricular fibrillation and modes of death in survivors of out-of-hospital ventricular fibrillation. We examined the causes of death in patients previously resuscitated from out-of-hospital ventricular fibrillation.  In 51 months, 234 patients were sucessfully resuscitated, hospitalized and discharged home.  During follow-up observation, 89 episodes of recurrent ventricular fibrillation or death (or both) occurred, 64 of which (72 per cent) were unexpected, out-of-hospital circulatory arrests.  Ventricular fibrillation occurred in 77 per cent of the 44 episodes in which the electrocardiogram was observed.  Ten patients survived one or more episodes of recurrent ventricular fibrillation.  Median time to recurrent ciruclatory arrest was 20 weeks after the preceding episode.  Prodromal symptoms were infrequent, and activity levels were generally low at the time of cardiac arrest.  Recurrent ventricular fibrillation of sudden death (or both) occurred predominantly when the initial episode was not associated with acute myocardial infarction.  Patients resuscitated from ventricular fibrillation are susceptible to early recurrence, probably reflecting continuing myocardial electrical instability.


Transbronchinal lung biopsy for the diagnosis of sarcoidosis. To evaluate the efficacy of transbronchial lung biopsy in the diagnosis of sarcoidosis, 26 consecutive patients with clinical features of sarcoidosis underwent this procedure during fiberoptic bronchoscopy.  In 21, the biopsy revealed noncaseating granuloma and, in the remaining five, normal lung parenchyma.  Subsequently, two of these five patients were found to have tuberculosis, one was confirmed as having sarcoidosis, and the fifth has not had further evaluation.  Transbronchial lung biopsy was therefore successful in the histologic confirmation of sarcoidosis in 21 of 23 patients.  The only complication was one 20 per cent pneumothorax, which resolved spontaneously.  Because of its low morbidity rate, high diagnostic yield and specificity transbronchial lung biopsy is recommended as one of the initial procedures for obtaining histologic confirmation in patients with suspected sarcoidosis.


Carcinoma of the urinary bladder in patients receiving cyclophosphamide. Hemorrhagic cystitis is a common side effect of cyclophosphamide therapy not observed with other alkylating agents.  In five patients receiving cyclophosphamide by mouth for prolonged periods with large cumulative dosage urinary-bladder tumors fatal to four and requiring cystectomy in the lone survivor developed.  These observations strongly suggest chemical carcinogenicity of this drug in the production of these tumors.  Increasingly, cyclophosphamide is being used for non-neoplastic disease.  These circumstances suggest careful follow-up observation of patients in whom hemorrhagic cystitis from this drug develops for evidence of bladder cancer, as well as restraint in use of cyclophosphamide for non-neoplastic diseases if alternative therapy is available.


[Serodiagnosis of human brucellosis].

[Serodiagnosis of human brucellosis]. On the basis of the serological study of 1000 sera obtained from patients suspected of suffering from brucellosis, the authors emphasis the theoretical data which confer upon this complement fixation reaction a greater reliability than the agglutination reaction. Using an appropriate antigenic preparation, the complement fixation reaction indeed proves to be of greater interest than the classical Wright sero-agglutination test in the diagnosis of brucellosis.


[Lupus nephropathy. Treatment with the indomethacin-hydroxychloroquine combination and comparison with corticoids]. The authors report their comparative experience of the treatment of proliferative lupus glomerulonephritis using prednisone (16 patients) or the indomethacin-hydroxychloroquine association (12 patients). Prednisone in high dosage was associated in this series with 9 deaths and in 6 patients, with renal failure or an extra-renal complication. By contrast, the indomethacin-hydroxychloroquine association proved to be highly effective, without side-effect. In the endocapillary glomerulonephritis group (8 cases) the authors obtained 7 durable remissions (36.3 months on average) and 1 temporary remission of 24 months, with an average length of treatment of 45.8 months. In the extracapillary glomerulonephritis group (4 cases) the authors obtained 1 remission, 2 improvements and I death, with an average length of treatment of 16.8 months. This combination has a highly significant anti-proteinuric and anti-haematuric action, with a constant efficiency on renal function and on the extra-renal signs of lupus. Its effect is less constant on the immunological disorders. Study of iterative renal biopsies confirms this favourable impression. According to these results, the authors propose a provisional scheme of management of proliferative lupus glomerulonephritis.


[Peri-osteocytic calcium fixation under calcitonin treatment. Microradiographic study using automatic analysis of images in 8 cases of osteogenesis imperfecta]. The authors treated eight cases of osteogenesis imperfecta using doses of 1 to 2 units of MRC over periods ranging from 6 weeks to 27 months. The lacunar surface area measured before and after treatment was greatly decreased as a result of the latter, probably as the result of marked calcium fixation around the osteocytes, though this effect seems to be transient. The hypothesis of an inactivation of calcitonin on a immunological basis or of a  secondary hyperparathyroid reaction is suggested.


A proton magnetic resonance investigation of the glycosyl torsion angle of uracil nucleosides and nucleotides. The use of line-shape decomposition techniques permitted the small 5-bond (5-J51') and 4-bond (4-J61') proton-proton coupling constants of a series of uracil nucleosides and nucleotides to be determined accurately. From an analysis of these coupling constants we have determined that the uracil base is in a predominantly anti conformation in aqueous solution and the mean position is not substantially altered by phosphate substitution at the 2', 3', or 5' positions, by changing the furanose stereochemistry from a ribose to a deoxyribose or an arabinose, or by an increase in temperature of 43 degree C.


A clarification of the complex spectrum observed with the ultraviolet circular dichroism of ethidium bromide bound to DNA. Ethidium bromide intercalation strongly effects the circular dichroism spectrum of DNA in the region of 230-300 mu, in a complex manner. In this report we present a study that quantitizes the relationships of the circular dichroism spectrum in the region of 230-300 mu and the ethidium bromide induced optical activity centered around 308 mu. We present evidence of two hidden cooperative bands that are probably the negative counterparts of the 308 mu band and 330 mu shoulder positive cooperative bands. The hidden band is quantitatively characterized. We confirm that the direct effect of ethidium bromide on the DNA spectrum is simply linearly proportional to the amount of intercalated dye. We also observe that the ethidium bromide enters freely when there is a molecule intercalated for every 3 sites, but that the intercalation is more difficult when the molecule intercalates at every second site.


A new method for mapping nucleic acid sequence homology by electron microscopy. We describe here a new method for the electron microscopic mapping of sequence homology in nucleic acids. Specific segments of the T7 chromosome have been isolated following digestion with the restriction endonuclease from Hemophilus aegyptious (Haey). Denatured segments are annealed to the l-strand of T7 DNA; treatment of the hybrid with glyoxal allows only guanosine residues in the single-chain region to the reacted, producing an adduct which will no longer hydrogen bond with its complement on the r-strand. When the segment is displaced and the glyoxalated l-strand allowed to renature with the r-strand, "H" shaped structures are produced in which the duplex region corresponds to the position of sequence homology with the segment. The conditions employed for glyoxalation do not detectably disrupt duplex regions as small as 400 base pairs. This procedure should be generally useful for observing sequence homology in more complex DNA molecules containing duplex regions which can be specifically enriched for and their arrangement determined by electron microscopy.


Influence of molecular weight of DNA on the determination of anti-DNA antibodies in systemic lupus erythematosus (SLE) sera by radioimmunoassay. Using a radioimmunoassay (RIA) based on the Farr technique with radioactively labeled 3-H-DNA for quantitative measurements of anti-DNA antibodies in sera of patients with systemic lupus erythematosus (SLE), the influence of molecular weight of DNA (ranging from 0.1 times 10-6 to 22.0 times 10-6 daltons) on binding and precipitation in this system has been investigated. Comparing our results with mathematical models it follows that one antibody molecule is fixed on the average to a statistical DNA segment of 2 times 10-6 to 4 times 10-6 daltons. Furthermore binding capacity of the DNA was found to be independent of the molecular weight, as demonstrated in a double label experiment using 14-C and 3-H-labeled DNA of different size. However, the amount of radioactivity precipitated was found to depend on the molecular weight of the labeled DNA following a non-linear function. It was calculated that a minimal ratio of fixed antibody molecules per a certain size of DNA was necessary for precipitation. The mathematical treatment of the observed non-linear precipitation dependence will be discussed using various statistical models. Our results indicate that the quantitative measurements of anti-DNA antibodies with the Farr technique e.g. for diagnosis and control of SLE in clinical immunology is highly dependent on the molecular weight of the labeled DNA used in the assay system and reliable results are only obtained with DNA of a sufficiently high molecular weight.


Thoracic and cervical myelography with metrizamide. Clinical experiences with a water-soluble, non-ionic contrast medium. One hundred cervical and thoracic myelographies were performed with the non-ionic, water-soluble contrast medium metrizamide. Good myelograms were obtained in almost all cases, adverse effects were minor, no serious complications occurred, and no convulsions were seen. Metrizamide is better than gas or isophendylate for demonstrating intraspinal expansive lesions of affections of the root sleeves.


Familial neuroblastoma presenting as multiple tumors. Multiple primary tumors are a common mode of presentation in familial neuroblastoma but must be differentiated from metastatic disease. The cases of 2 siblings with multiple neuroblastomas are presented and 44 additional cases of neuroblastoma reviewed. It was found that primary tumors localize to the posterior mediastinum, the adrenals, and the paravertebral ganglia whereas metastatic disease is found in the anterior and middle mediastinum, bones and para-aortic nodes. Based on these observations, the diagnosis of multiple primary tumors can be made and should lead to early consideration of familial neuroblastoma.


The "patellar ratio" in hemophilia and juvenile rheumatoid arthritis. The ratio of patellar length to width was analyzed in comparison with subjective examination using radiographs of the affected knees in patients with hemophilia, juvenile rheumatoid arthritis (JRA), and controls to determine the usefulness of this measurement in differentiating the two diseases. A statistically significant difference was found between the proportion of JRA patients, controls, and patients with hemophiliac arthritis involving the knee. It was difficult to distinguish hemophilia from JRA by subjective analysis of the appearance of the knee using standard criteria. The patellar ratio is a more objective criterion which should be helpful in the radiological differentiation of JRA from hemophilia affecting the knee.


Mangement of squamous cell carcinoma of the oral tongue and floor of mouth after excisional biopsy. A review of the records of 23 patients with squamous cell carcinoma of the oral tongue and floor of mouth treated with irradiation after excisional biopsy has shown that: (a) Radiotherapy, primarily using interstitial radium implants, results in excellent local control of the primary area (100%) with preservation of function. (b) The frequency and severity of soft-tissue and bone necrosis may be reduced by not exceeding 5,500-6,000 rads from radium implants when only subclinical aggregates of cancer cells are probably present. (c) Theincidence of subsequent neck disease is low-8.7% (2 of 23 patients), and does not warrant routine elective irradiation of the cervical lymphatics.


Optimization of dose distributions in moving-strip therapy using a minicomputer. Optimized 60-Co dose distributions for the moving-strip technique were calculated for 3 patients using a PC-12 minicomputer program which corrects for field obliquity and changes in patient thickness. Beam profiles were measured using an ionization chamber in a water phantom. A Masonite phantom was constructed to simulate a patient and used to measure optimized and unoptimized midplane dose distributions by thermoluminescent dosimetry. Measured midplane doses agreed with computer-calculated doses within experimental error. The computer optimization technique improved dose uniformity, reducing the midplane dose variation from plus or minus 12-13% to plus or minus 3-4%.


Endothelial repair of radiation damage following beta irradiation. Lamellar keratectomy was performed in dogs to induce capillary endothelial proliferation at the limbus of the eye and the radiation response of endothelial cells was evaluated in terms of the dose required to prevent neovascularization in 50% of irradiated eyes (NVD50).Single- and split-dose experiments were carried out before and after induction of proliferation to determine the response of slowly and rapidly proliferating endothelial cells. the NVD-50-S prior to induction were about 400 rads greater than those following induction,indicating increased resistance of slowly proliferating cells. Split-dose studies indicatedthat the radiation repair capability was about 350 rads, either before or after induction.


Spatial distribution of effects of negative poins on cultured human cells. Cultured human kidney T-1 cells were irradiated in flasks or on coverslips at different depths in a water phantom using the Los Alamos Meson Physics Facility Biomedical negative pion beam. Postirradiation colony formation and cell multiplication were assayed. Maximum cell inactivation occurred in the vicinity of maximum pion dose. Comparison of dose-survival curves with those found following x irradiation indicated RBE = 1.4 plus or minus 0.3 for colony formation and approximately 1.5 for growth delay. Delivery of 400 pion rads in four fractions resulted in higher survival than did delivery of 400 rads in a single fraction.


Radiology of the Swan-Ganz catheter and associated pulmonary complications. Radiographic features of the Swan-Ganz catheter and the complications associated with its use are described. Pulmonary infarcts develop subsequent to wedging of the catheter in a peripheral position, failure to deflate the balloon after use, and maintenance for morethan 72 hours. The radiology of the infarct is usually classical in appearance, i.e., pleural-based density which resolves in 14-21 days. The frequency of pulmonary ischemia may BE related to compromise of the venous and collateral arterial circulation in intensive care unit patients in whom the catheter is used.


Biological effects of the Los Alamos meson beam on cells in culture. Preliminary measurements of the biological effects of negative pions on cells in culture are reported. Cell survival as a function of depth was obtained by using gelatin to suspend the cells. The results indicate that the effects are more pronounced at the peak portion of negative pions. Cell-survival curves were also obtained under oxygenated and hypoxic conditions. The biological effectiveness at the peak was found to be a factor of 2.0 higher than at the plateau. The oxygen enhancement ratio was 1.5 at the peak. No significant differences in biological effects were observed above 14 mm in the peak region.


Effects of contrast agents on the blood-brain barrier. An electron microscopic study. To determine if contrast agents after the blood-brain barrier by opening tight junctions between endothelial cells and by increasing pinocytosis, the distribution of horseradish peroxidase (HRP) was evaluated after intracarotid injections of contrast media. HRP did not cross the endothelium of cerebral blood vessels. Tight junctions remained closed. There was increased endothelial cell pinocytosis and swelling of astrocyte end-feet.


Small bowel biopsy by coaxial catheter. A simple, rapid technique. A new small intestinal biopsy technique was developed and evaluated: it involves the rapid replacement of a simple duodenal tube using a controllable spring guide and fluoroscopy. A suction biopsy catheter was then passed coaxially through the tube as often as needed for sampling, after which other diagnostic studies were done with the same intubation. In clinical trials totaling 31 biopsies in 15 adult patients, the method proved safe and effective. Currently, the time required to intubate the ligament of Treitz and obtain two biopsies is usually less than 15 minutes.


Evaluation of a videodensitometric method for monitoring the left ventricular contractile state. Videodensitometry of the margins of the fluoroscopic image of the left ventricle (LV) was used to evaluate LV wall motion. Differentiation of the wall motion signal reflected the velocity of LV contraction (dv/dt) during various inotropic interventions in 6 anesthetized dogs. Alterations in dv/dt were similar to changes in simultaneously measured LV peak dP/dt and the quotient of dP/dt and developed LV pressure, two widely accepted parameters of LV contractile state.


Prostaglandin E1 as a pharmacoangiographic agent for arterial portography. The effects of increasing single selective doses of prostaglandin E1 (PGE1) on superior mesenteric arterial flow and portal and systemic blood pressures were studied in dogs to assess its value as a vasodilatory agent for pharmacoangiography. PGE1 consistently increased blood flow, with an average increase of 187%, but had minimal effect on portal and systemic blood pressure. 25 mug of PGE1 gave an ideal flow curve for pharmacoangiography, with a maximum effect 30 seconds after injection.


An animal model of radionuclide venography. Experimental venous thrombi were created in 19 dogs, using either thrombin or sodium morrhuate. Eighteen thrombi (95%) were identified by radionuclide venography; however, an 85% false-positive rate was found when nonoperated limbs were studied. The models employed were considered unsuitable for studying the accuracy of labeled particles in diagnosing deep venous thrombosis for the reasons discussed in the text.


A new method for determining the neutron response function of "neutron insensitive" dosimeters. Method and preliminary determinations. Charged-particle bombardment of thick beryllium targets produces a neutron yield varying with angle, and an isotropic gamma component. Differences in detector response in such a field are due to neutrons alone. With accurate neutron spectral distributions and measurements of detector response, a computer code can be used to determine the neutron sensitivity of the detector as a function of energy.


Lateral projections with inclined head for angiography of basal cerebral aneurysms. Inclined lateral projections prove useful in defining aneurysms situated about the circle of Willis. For these projections, the x-ray tube and film changer are positioned as for a true lateral projection. The MCA lateral projection (patient's head inclined away from the side of injection) is valuable in investigating aneurysms of the internal carotid artery, posterior communicating artery and middle cerebral artery trifurcation. The ACA lateral projection (head inclined toward the side of injection) may be used to define aneurysms in the region of the anterior communicating artery.


Preparation, quality control and clinical acceptance of labeled Macrotec. Thirty minutes after reconstitution, radiochemical purity determinations of the lung-scanning agent Macrotec (99m-Tc-MAA) indicated 95-100% technetium labeling: 76% of the particles had a mean diameter of 10-50 mu. Rat tissue distribution studies indicated lung uptake of 98% at 15 minutes. The biological half-life in the lung was 8.3 hours. In 12 patients requiring emergency lung scans, 9 scans were rated excellent. No liver, spleen or thyroid uptake or adverse reactions were noted.


Editorial: Guidelines for radioactive tracer studies of the heart and circulation. Report of the Inter-society Commission for Heart Disease Resources. The Inter-Society Commission for Heart Disease Resources report concerning optimal resource guidelines for radioactive tracer studies of the heart and circulation is described. This report is an overview of the status of cardiovascular radionuclide diagnostic studies as well as a guideline to the hospital resources (physical and human) required for a high-quality nuclear medicine laboratory dealing with this area of study. These guidelines are directed to physicians and hospital administrators who are currently responsible for planning and organizing nuclear medicine programs or who anticipate a future need for such services in their community.


Interpretation of roentgenograms via interactive television. The diagnostic quality of roentgenographic images transmitted by interactive television was evaluated. A series of 100 kidney, ureter and bladder, chest, and bone radiographs were read individually by five radiologists, both on direct viewing and on viewing a monitor image of the television signal. The latter was transmitted by microwave a distance of 28 miles, including four transmission legs. Analysis in terms of receiver operating characteristic curves and critical tables indicated that the television interpretations were of acceptable accuracy, in view of the participants' inexperience with teleradiology.


Angiographic findings in multiple bile-duct hamartomas of the liver. The angiographic appearance in a patient with multiple bile-duct hamartomas of the liver is described. The lesions showed abnormal vascularity, consisting of grapelike clusters of small rings, which could be confused with other benign and malignant conditions demonstrable by angiography; however, it may ultimately prove to be characteristic of this uncommon lesion. The angiographic differential diagnosis is discussed.


The clinical indications for arteriography in trauma to the extremity. A review of 114 cases. Analysis of radiographic and physical findings in 114 patients with trauma to an extremity demonstrated that when other physical findings are normal, arteriography is unnecessary. If any physical sign of peripheral vascular injury exists, such as weak or absent pulse, neurologic deficit, bruit, or expanding hematoma, arteriography is essential to define the anatomy and determine the need for surgery.


Contraction of the canine gallbladder in different degrees of common bile duct obstruction. C-terminal octapeptide of cholecystokinin was administered at six dose levels, 4-128 ng/kg, by 184 intravenous injections to three mongrel dogs under several pressure conditions of the biliary system. Gallbladder contraction was monitored radiographically. A good, dose-dependent contraction response resulted with intraductal pressures of 0 and 10 cm water. At 20 cm water, a markedly reduced and dose-independent response occurred. No contraction response was found with an intraductal pressure of 30 cm water. This animal experimental work suggests that in man, a contraction response of 30% or more may rule out significant common bile duct obstruction.


Roentgenographic measurement of skin thickness in normal individuals. A CGR mammographic unit was modified to provide a more accurate method of measuring skin thickness. Evaluation of 418 normal patients indicated that skin thickness is greater in men than women, is less in older individuals, and, to a less extent, is greater in more obese patients. Height and race do not have a statistically significant bearing on skin thickness values. These "normal" values may prove useful as a screening criterion in evaluation of patients with possible acromegaly or Cushing's syndrome. Other potential applications are being investigated.


Coracoid process fracture diagnosis in acromioclavicular separation. Three cases demonstrating avulsion of the coracoid process from the scapula associated with acromioclavicular separation are presented. Two patients were adolescents and one a young adult, suggesting that the coracoid base epiphyseal plate in this age group may be weaker than the coracoclavicular ligaments. A cranially-angled view of the shoulder was diagnostic in two cases. Recognition of this condition is mandatory if the orthopedist is planning fixation of the clavicle to the coracoid to remedy an acromioclavicular separation.


Ruptured corpus luteum with hemoperitoneum. Rupture of the corpus luteum in a young woman can cause massive hemoperitoneum, seen as free fluid in the flanks and pelvis on abdominal films. Radiographic examination alone cannot distinguish hemorrhage due to a ruptured corpus luteum or ectopic pregnancy from pus due to a ruptured appendix or a tubo-ovarian abscess; however, the presence of nonclotting blood on culdocentesis excludes abdominal sepsis. If these symptoms and findings occur during the latter half of the menstrual cycle in a young woman of low parity who has a normal menstrual history and a negative pregnancy test, a ruptured corpus luteum is a more likely diagnosis than ectopic pregnancy.


Emergency room radiology: a format for instructing house staff. Seminars covering the use of radiographic studies in the emergency room were given to the house staff. Greater efficiency in ordering indicated studies was achieved, and fewer repeat studies and unnecessary radiographic examinations were ordered. In addition, the radiologist and his staff became more aware of clinical problems in the emergency room. The authors feel that a series of seminars of this type can have a beneficial effect on general patient care.


Anterior inferior cerebellar artery originating from the cavernous portion of the internal carotid artery. An anomalous branch of the cavernous carotid artery, not reported previously, is described. Its appearance and distribution were unlike those of any known cavernous branch, originating at the level where the trigeminal artery is usually found but having no communication with the basilar artery. Its distribution approximated that of the anterior inferior cerebellar artery. The author believes that this is an unusual form of persistent embryonic communication between the carotid artery and the vessels of the posterior fossa.


Multiple sites of interaction between prostaglandins and non-steroidal anti-inflammatory agents. Several non-steroidal anti-inflammatory agents (NSAIA) are shown to inhibit the net production of prostaglandin (PG)- like activity from arachidonic acid by a cell-free preparation of guinea-pig lung. Moreover, these agents also antagonize PGE-1-induced contractions of the isolated gerbil colon. The anti-spasmogenic effects are reversible and specific. At high concentrations, indomethacin and mefenamic acid interfere with the binding of PGE-1 to a broken cell preparation of rat epididymal adipocytes. Taken together the data indicate that NSAIA interact with prostaglandins at multiple sites and are consistent with the suggestions reported previously that NSAIA may have multiple in vivo actions.


Effects of prostaglandin antagonist SC-19220 on body temperature and on hyperthermic responses to prostaglandin E-1 and leukocytic pyrogen in the cat. Intravenous injection of SC-19220 (3-9 mg/kg) caused dose-related hypothermic responses in cats. Repeated administration of SC-19220 resulted in tolerance to its hypothermic action. During SC-19220-induced hypothermia, the hyperthermic activity of both prostaglandin E-1 and leukocytic pyrogen was reduced or abolished. Neither prostaglandin E-1 nor leukocytic pyrogen was antagonized when given shortly after recovery from SC-19220-induced hypothermia or by doses of SC-19220 which did not cause hypothermia. Although these results may indicate a role of prostaglandins in normal physiological thermoregulation, it is also possible that production of hypothermia by SC-19220 is unrelated to prostaglandin antagonism.


15-Methylation augments the cardiovascular effects of prostaglandin F-2alpha. Intramuscular injection of the 15-methyl analogue of prostaglandin F-2alpha (15-ME-PGF-2alpha) is being used to initiate second trimester abortion. The natural prostaglandin F-2alpha (PGF-2alpha) is a known pulmonary pressor agent but there is little information about the cardiovascular effects of the analogue. Consequently, we compared the hemodynamic responses to the two forms in twenty-three anesthetized dogs. Given I.M. or I.V. 15-me-PGF-2alpha produced a greater and more sustained rise in pulmonary arterial pressure than PGF-2alpha. Intramuscular 15-me-PGF-2alpha also elicited a more prolonged increase in pulmonary vascular resistance than prostaglandin F-2alpha given I.M. or I.V. The methyl analogue (I.M. or I.V.) causes a greater initial fall in systemic arterial oxygen tension and cardiac output, and a greater increase in systemic resistance than I.M. PGF-2alpha. Breathlessness seen during abortion induced by prostaglandin F-2alpha or its methyl analogue may be caused by acute pulmonary hypertension in addition to bronchoconstriction.


Modulation by prostaglandins of contractions in guinea-pig ileum. A high concentration of indomethacin (40mu-g/ml) substantially reduced contractions of guinea-pig isolated ileum in Krebs solution to nerve stimulation with electrical pulses or nicotine. Responses to acetylcholine and histamine were also inhibited, but to a smaller extent. Low concentrations of prostaglandin E-2 (2 or 4ng/ml) mainly restored all the excitatory responses. Using a modified bathing solution (lacking in phosphate and with some other changes) indomethacin 0.36mu-g/ml selectively inhibited nerve-mediated contractions. The results explain differences in various reports, and support the possibility that prostaglandins modulate the response to cholinergic nerve activity.


Effects of indomethacin on venoconstrictor responses to bradykinin and norepinephrine. In order to determine whether the venoconstrictor response to BK was dependent on prostaglandin (PG) synthesis, effects of indomethacin (INDO) on responses to bradykinin (BK) and norepinephrine (NE) were studied in canine lateral saphenous vein. Cumlative dose-response curves (10-9-10-6M BK or NE) were done in the presence and absence of INDO (10-6M). In the presence of INDO, responses to BK were markedly enhanced while responses to NE were unchanged. After prolonged periods in the bath, responses to BK were enhanced in control strips while responses of strips which had been treated with INDO were depressed. These results suggest that BK does not normally cause venoconstriction by stimulating synthesis of a venoconstrictor PG and that the increase in response to BK after prolonged periods in the bath may be related to changes in PG synthesis.


The synthesis and biological activity of alkyloxy prostaglandin analogues. Prostaglandin analogues in which the alkyl chain attached to C-15 in the natural compounds is replaced by an alkyoxyalkyl group have been synthesised. Compounds of the 17-oxa series are particularly potent luteolytic agents and are selective in the sense that they are less effective than PGE-2alpha in causing isotonic contractions of isolated uterus muscle.


A mass fragmentographic method for the quantitative evaluation of brain prostaglandin biosynthesis. A method for the evaluation of PGF-2alpha and PGE-2 biosynthesis in rat cerebral cortex is described. Tissue slices were incubated without any added precursor for different lengths of time. The analytical procedure involves prostaglandin extraction, purification and quantitative determination by mass fragmentography. Significant amounts of both prostaglandins were synthesized. The biosynthesis reached a plateau after 30 minutes and the ratio of PGF-2alpha to PGE-2 was approximately 3.


The effect of intra-uterine prostaglandin F-2alpha on corpus luteum function in the human. Prostaglandin F-2alpha (PGF-2alpha) was administered via a Foley catheter over a 12 hour period to 8 healthy volunteers awaiting laparoscopic sterilisation. The amount of PGF-2alpha infused varied between 500 mu-g and 2000 mu-g every 2 hours for 6 doses. Plasma progestins and oestradiol 17beta, and urinary estrogens and pregnanediol were assayed throughout the study period. There was no evidence of luteolysis in any patient although vaginal bleeding of varying duration occurred in all women within 36 hours of administration of PGF-2alpha.


Assessment of possible luteolytic effect on intra-ovarian injection of prostaglandin F-2ALPHA in the human. A group of five patients awaiting laparoscopic tubal diathermy were followed by daily assay of luteinising hormone (LH) and progesterone. Between five and eight days after the LH peak, prostaglandin F-2ALPHA (PGF-2ALPHA) was injected into either the corpus luteum or the ovarian stroma. Doses of 100 mu-g into the corpus tuteum, 1000 mu-g into the adjacent stroma and 500 mu-g into an indeterminate ovarian structure had no effect on peripheral plasma progesterone levels or uterine bleeding. An injection of 500 mu-g or 1000 mu-g given unequivocally into the corpus luteum produced a rapid and profound fall in plasma progesterone levels, the nadir coinciding with the onset of uterine bleeding which commenced 24 hours after the injection and persisted for more than seven days. Injection of 100 mu-g in the same volume of saline had no such effect. Despite continued bleeding plasma progesterone levels returned to normal luteal levels for three days and then fell again.


Effects of prostaglandins E-1 and F-2ALPHA on serum luteinizing hormone concentration and on some sexual functions in male rabbits. PGE-1(50 mu-g/animal) and PGF-2ALPHA (250 mu-g/animal) caused a transient increase in serum LH at 5 min after injection. PGE-1(250 mu-g/animal) had a biphasic effect on serum LH. A small peak was obtained at 5 min, and a second, larger peak at 60 min after injection. It is suggested that the first peak is a result of the stress associated with injection of the PGs, whereas the second peak represents a physiological effect of PGE. Subcutaneous injection of PGE-1(1 mg in arachis oil b.i.d.) for 10 days did not effect the concentration of LH in serum, the function of the accessory sexual glands or the sexual activity. PGF-2ALPHA, given at the same dose and in the same manner, increased the sexual activity but left all other variables unaffected. The pituitary responsiveness to LH-RH was unaltered by the treatment with PGE-1 and PGF-2ALPHA.


The excretion of prostaglandin F-2ALPHA in milk of cows. Prostaglandin F-2ALPHA (PGF-2ALPHA) was measured by immunoassay in plasma and milk of four cows (six experiments). After 30 mg PGF-2ALPHA im, plasma PGF-2ALPHA peaked at 15 minutes (2.4 plus or minus 0.7 ng/ml) and declined toward basal values by 3 hours; maxiumum milk PGF-2ALPHA (0.91 plus or minus 0.12 ng/ml) occurred at 1 hour. The average excretion rate in milk was 2.9 mu-g/day 0.9 mu-g (0.003%) of which was due to the 30 mg PGF-2ALPHA injected. In six nonpregnant control cows, daily changes of milk PGF-2ALPHA and progesterone were not consistently related.


The relaxant property of local prostaglandin E-2 on the non-pregnant uterus - a cyclic triphasic response. The response of the non-pregnant human uterus to intravenous (i.v.) injections and intra-uterine instillation of various doses of prostaglandin E-2 (PGE-2) was evaluated at the different phases of the menstrual cycle in 13 fertile regularly menstruating women who were neither lactating nor using any hormonal therapy. Uterine contractility was recorded by the microballoon technique in at least three sessions(proliferative, mid-cycle and secretory) in a single cycle with endometrial biopsy performed immediately following the last session to ascertain that the particular cycle was an ovulatory one. Single i.v. injections of PGE-I had a consistent stimulatory effect on the contractility throughout the cycle with a tendency towards a decreased uterine response at mid-cycle and luteal phase as compared to the proliferative part of the cycle. Intra-uterine instillation of the compound induced a peculiar and interesting type of response. In the proliferative and secretory phases of the cycle the response was one of stimulation; being more pronounced in the former period. However, around ovulation time, the local administration induced an evident uterine relaxation in most cases without any instance of stimulation. The possible implication of this triphasic response behaviour on the non-pregnant uterus within certain physiological events and pathological conditions is discussed.


Termination of second trimester pregnancy with intra-amniotic 15 (S) 15 methyl prostaglandin F-2alpha - a two dose schedule study. Termination of second trimester pregnancy with intra-amniotic administration of 15 (S) 15 methyl prostaglandin F-alpha (15 me F-alpha) was attempted in fifty patients. One group (26 patients) was given 1 mg of the analogue and the other group received 2.5 mg. The abortifacient efficacy of 15 me F-2alpha was similar in both groups; over 90% of the patients aborted with a single dose. There was a higher incidence of vomiting, diarrhoea and incomplete abortions in the group treated with 2.5 mg 15 me F-2alpha. Although the mean injection-abortion interval in the 2.5 mg group was shorter, it is concluded that intra-amniotic administration of 1 mg 15 me F-2alpha provides a better regime, giving high efficacy with a single dose, a low incidence of side effects and greater safety in case of inadvertent entry of the intra-amniotic dose into systemic circulation.


Midtrimester pregnancy interruption and the placental progesterone levels. Placental progesterone contents were studied in 10 patients therapeutically aborted at midtrimester by intraamniotic infusions of hypertonic saline, and from 14 patients (12-20 weeks) aborted by intraamniotic instillation of prostaglandin F-2alpha. The mean S.E. of the progesterone was 1.99 plus or minus 0.07 ug/g. placental tissue in the first group, while with prostaglandin abortion the placental progesterone was 1.45 plus or minus 0.08 ug/g. tissue, which is significantly lower than the results in the first group (P equals 0.001). The possible mechanism of action of prostaglandin as an effective abortifacient is discussed.


Prostaglandins F in uterine and ovarian venous plasma from nonpregnant and pregnant ewes collected by cannulation. Periodic collections of uterine venous blood were obtained from three nonmated, three pregnant and two mated but nonpregnant ewes in which uterine veins were cannulated with polyvinyl tubing on day 11 postestrus. Frequent sampling was achieved in three of these ewes with additional cannulae in the ovarian veins. Blood samples were collected at 3-hr intervals from 0600 on day 12 to 1800 on day 13 and then 6-hr intervals through day 15. On day 13, three additional samples at 30-min intervals were collected between 1400 and 1530. Prostaglandins F (PGF) in plasma were quantified by radioimmunoassay. On day 12, one ewe in each group had at least one measurement which suggested an increased rate of release of PGF into the uterine vein. Seven of eight ewes on day 13 appeared to have increased rates of release of PGF from the uterus between 0900 and 1500. The highest level measured in each ewe during this period ranged from 2.7 to 11 ng per milliliter. Concentrations of PGF in ovarian venous plasma in two of three ewes were positively correlated (P less than .05) with concentrations of PGF in uterine venous plasma (r equals .64 in each ewe). No evidence was obtained that pregnant and nonpregnant ewes differ in rate or pattern of release of PGF from the uterus into the uterine vein on days 12 and 13. Comparisons could not be made with confidence concerning PGF either in uterine veins on days 14 and 15 or in ovarian veins on all days due to limited number of observations.


[The effect of severity and duration of hemorrhagic hypotension and the narcosis on the plasma levels of lysosomal enzymes in dogs (author's transl)]. The effect of degree and duration of hemorrhagic hypotension on the lysosomal enzyme and LAP levels of plasma of the anaesthesied or wakeful dog has been examined. We ascertained that in a state of hypovolaemia a reduction by 10 mm Hg of the blood pressure resulting significantly increased enzyme activity during the same time. A similar change was caused by prolonging the time. In the anaesthesised group there was the enzyme activity after 120 min of haemorrhagic hypotension lower.


[Influence of L-thyroxine upon the ratio between protein-bound SH- and S-S-groups (author's transl)]. In normal rats and in rats with mercury-induced tubular lesions without or with successive L-thyroxine treatment, the number of SH-groups and the total of SH- and S-S-groups in different segments of the nephron were calculated over a period of time by means of a photometric assay. The quantity of SH-groups was increased by low doses of sublimate but reduced by exogenous L-thyroxine, the whole of SH- and S-S-groups summing up to a constant quantity throughout. (Following application of high doses of sublimate, a loss of SH- as well as S-S-groups was observed, due to cellular destruction.) Connection and splitting of S-S-bridges, respectively, corresponded to changes in certain parameters of cell function, for instance resorptive capacity. A hypothesis is proposed stating that a fundamental effect of thyroid hormone is exerted by a biochemical action upon the ration between SH- and S-S-groups, permeability of the cellular and mitochondrial membranes being raised when the numerical proportion of S-S-bonds is high. Stimulation of enzymatic activity and metabolic processes would therefore result adaptively from the augmentation of substrate supply within the cell organells.


Protein absorption from the perricardial cavity. The absorption of radioactive labeled protein from the pericaridal cavity and from the parietal and visceral membranes of the pericardium was investigated in 49 dogs. The absorption of 1 ml/kg injected diluted dog serum is slow (T1/2 About 24 hrs). The rate of protein absorption, particularly of the lymphatic transport, is lower from the parietal pericardium than from the epicardium. About 35 to 50% of the protein absorbed from the pericardium is removed by the blood capillaries, the rest by the lymphatic system. The major part, about 60%, of the protein absorbed by the lymphatics is transported by the cardiac lymph vessel, the remainder by lymphatics joining the great veins on the right side of the neck. The thoracic duct plays only an insignificant part in the transport of protein from the pericardial cavity.


The metabolism and organ distribution of 5,6-trans-25-hydroxycholecalciferol, an analog of vitamin D-3 in vitamin D-deficient rats. Investigations have been performed on the metabolism and organ distribution of 5,6-trans-25(OD)D-3, which represents an analog of vitamin D-3 being active in uremia. This analog is rapidly metabolized into at least two more metabolites. The main storage organ for this compound seems to be fat, whereas liver and intestinal mucosa showed at 24 hrs the highest concentration of polar metabolites. In contrast to 25(OH)D-3 5,6-trans-25(OH)D-3 is much less absorbed from the intestinal tract, which should be considered if this compound is applied for treatment of uremic bone diseases.


[The function of the isolated heterologous liver perfused with the human blood (author's transl)]. The metabolic changes and their influence on the isolated liver were studied in 21 experiments on pig liver, perfused with human blood during the period of 3 hrs. It was detected, that rather active carbohydrate and nitrogenic metabolism has been maintained in the liver during 1.5-2 hrs. But after the 2nd hr of perfusion the phenomens of perfusion the phenomens of hypoxia increased, that caused the inhibition of metabolic processes and leaded to deterioration of liver function. The experience of clinical perfusions showed, that the functional activity of assisted liver over the period of 90 min was so depressed, that the organ couldn't provide positive clinical effect.


[Insorption of tritiated water in hepatic cirrhosis (author's transl)]. In 10 patients with hepatic cirrhosis of various etiology both the insorption and the volume of distribution of tritiated water are determined. Indicator for the velocity of insorption is the time interval between the oral application of 200 mu-Ci THO distributed in 100 ml tap water and the appearance of a peak concentration of the isotope in the serum. In comparison with normal controls the insorption of THO is protracted in patients with hepatic cirrhosis from 37.0 plus or minus 4.4 min (S.E.) to a mean of 69.0 plus or minus 29.6 min. Individually the "insorption time" can be quite normal. The prolongation of the process of insorption is independent of the apparent volume of distribution of THO or of the etiology of hepatic cirrhosis. In the early phases of the insorption which are characterized by the main increase of the radioactivity in serum there is no difference between patients with hepatic cirrhosis and normal controls. Although an alteration of body fluid metabolism can not be excluded as a source of the prolonged equilibration, it is suggested that changes of the intestinal blood flow, of the tissue pressure and of the colloidosmotic pressure are due to a disturbance of the insorption of tritiated water in patients with hepatic cirrhosis.


The incidence of gastric ulcer in Copenhagen county. A regional epidemiological investigation comprising one-tenth of the Danish population showed the annual incidence of new gastric ulcers during the period 1963-68 to be 0.44 per 1000 inhabitants aged 15 years and over. The corresponding incidence of solitary ulcers among former 'non-ulcer' patients was 0.31 per 1000. Similar incidence rates have been registered in comparable investigations from other Northern European countries within the last decades. The disease appears, however, to be relatively more frequent in Danish women than in women elsewhere, excluding in Australia. The annual incidence varied, but no indications of a systematic trend was registered. In solitary ulcers the ratio male: female was 1.1:1, while it was 2.2:1 in the cases in which a duodenal ulcer had been demonstrated, earlier or simultaneously with the gastric ulcer. The age incidence was identical for the two categories of patients. In both groups a considerable rise in the incidence was registered only in age groups above 40 years. In men the incidence was maximal for the 60-64 year age groups, while in women it increased with increasing age. The age-specific incidence rates of diagnostication as well as of symptomatic debut did not vary significantly according to the localization of the lesion.


The effect of the site of lesion and extent of resection on duodenal bile acid concentration and vitamin B12 absorption in Crohn's disease. Duodenal bile acid concentration following a standard meal, glycine/taurine (G/T) ratio, vitamin B12 absorption, and faecal fat were determined in 79 patients with Crohn's disease. Intestinal resection had been made in 50 patients before the study, and no evidence of recurrence was present at the time of the study. Among 46 patients subjected to ileal resection of 10-180 cm, a reduced duodenal bile acid concentration and vitamin B12 malabsorption was almost invariably present when 50 cm or more of ileum had been removed. Patients with smaller resections and unoperated patients did not show a consistent pattern. Vitamin B12 absorption and duodenal bile acids were of equal value as indicators of ileal dysfunction with the exception that, in 10 ileostomy patients, duodenal bile acids were decreased in every case, but vitamin B12 absorption only when 80 cm of ileum or more had been resected. G/T-ratio was related to the extent of ileal resection-being elevated after large resections (80 cm or more)-but not to the presence of an abnormal flora. Faecal fat was much more elevated in ileostomy patients with large ileal resection (80 cm or more) than in unoperated patients and patients without an ileostomy.


Chronic persistent hepatitis. A clinical, serological, and prognostic study. The diagnosis of chronic persistent hepatitis is based on a combination of clinical and morphological data. During a 7-year period 26 cases were diagnosed in 3 medical departments in Copenhagen. In 22 patients the disease was considered to be a sequela to acute viral hepatitis, and 12 had Australia antigen in serum. Only few patients had circulating auto-antibodies. The clinical and biochemical activity at the time of diagnosis was usually slight. A morphological and clinical follow-up study revealed that the course of the disease was generally benign. However, in 3 patients the last repeat biopsy showed progression to cirrhosis, severe portal fibrosis, and chronic aggressive hepatitis. Such exceptions may represent a sampling error in the interpretation of the first needle biopsy, or the correct diagnosis may have been chronic aggressive (active) hepatitis at a stage with slight activity. Clinical and biochemical observation is recommended in chronic persistent hepatitis, and in some patients serial needle biopsies are necessary to reveal the few exceptional cases which progress to an active chronic liver disease.


The effect of cholecystokinin on electrical spike potentials and intraluminal pressure variations in the human small intestine. Electrical spike potentials and intrauminal pressure variations were recorded from the human duodenum and distal ileum before and after i.v. administration of 80 log Ivy units of cholecystokinin. In the duodenum, quantitative calculations of motility gave identical values before and after drug administration, and results were identical in patients before and after cholecystectomy as well as in hernia patients without upper gastrointestinal disease. A decrease in amplitude of the spike potentials was observed in the duodenum during the first few minutes after drug administration in all groups. Recordings from the distal ileum in ileostomy patients showed a significant increase in motility after CCK administration whereas the spike potential amplitude was unchanged.


The incidence of lactose malabsorption in ulcerative colitis. 120 Danish patients with ulcerative colitis, admitted consecutively to a Department of Gastroenterology, were investigated for lactose malabsorption. The prevalence was 9.2 percent, which is not significantly higher than that in a mixed Danish gastroenterological material, There was no difference in distribution according to age and sex, and the incidence was not correlated to the severity of the ulcerative colitis. The possible reasons for the wide variation in the incidence of lactose malabsorption in materials of patients with ulcerative colitis are discussed, and it is concluded that the main cause  must be that the materials with the highest incidence include patients of races and ethnic groups in which lactose malabsorption is a common finding.


Increased plasma gastrin levels in connection with inhibition of gastric acid responses to sham feeding following bulbar perfusion with acid in dogs. Dogs were provided with oesophageal fistulae, fully innervated pouches of the fundic stomach and the duodenal bulb, and a gastric cannula. Gastric secretion was stimulated by sham feeding for 10 min. The bulbar pouches were perfused either with 0.9 per cent NaCl or with 0.1 N HCl. Plasma gastrin concentrations were determined by radioimmunoassay. Bulbar acidification effectively inhibited gastric acid secretion. Plasma gastrin responses were not suppressed. Instead, plasma gastrin concentrations were higher than in controls. The results show that the bulbar mechanism does not inhibit gastric acid secretion by reducing gastrin release.


Effect of bulbar perfusion with acid, hypertonic solutions, and acetylcholine on gastric acid secretion in dogs. Dogs were provided with innervated pouches of the fundic stomach and the duodenal bulb. One dog also had an isolated pouch of the distal duodenum. Acid secretion was stimulated by intravenous infusion of a low dose of pentagastrin (ICI 50 123). Bulbar pouches were perfused with solutions of 0.9% Na C1, 0.1 N HC1, 40% glucose, 40% NaC1, and 40% peptone or with 0.1% solutions of acetylcholine chloride. Acidification of the bulbar pouches profoundly inhibited the acid output from the gastric ppoches. Perfusion with acetylcholine produced a transient inhibition of acid secretion. When hypertonic solutions were perfused through the bulbar pouches or the pouch of distal duodenum, no inhibition occurred. It is concluded that hypertonic solutions are not activators of the bulbar inhibitory mechanism that has been shown to respond to reduction of the intrabulbar pH. Inhibition following bulbar perfusion with acetylcholine may mean that liberation of the hypothetical humoral agent, bulbogastrone, to some extent is under cholinergic control.


Effect of 16,16-dimethylPGE2 on gastric emptying and intestinal transit of a barium-food test meal in man. The effect of 140 mug of 16,16-dimethyl PGE2 on gastric emptying and intestinal transit of a barium-food mixture has been studied in 8 healthy male volunteers. The propagation of the test meal was followed from the stomach to the colon by fluoroscopy wit repeated photograph ic recording. It was found that this analog significantly enhanced the rate of gastric emptying in most subjects, and the food-contrast medium also appeared sooner in the colon following the prostaglandin analog. In addition, the duodenum and the first part of the jejunum had a flaccid and dilated appearance on several occasions after administration of prostaglandin. The more rapid emptying of the stomach after administration of the prostaglandin analog is probably explained by a decreased duodenal resistance towards the gastric outflow; the earlier appearance of contrast in the colon could partly be due to the more rapid gastric emptying following administration of the prostaglandin analog.


Liver failure and drug metabolism.

Liver failure and drug metabolism. The hepatic microsomal metabolism of antipyrine, as measured by its metabolic clearance, was investigated in 18 patients either before, during, or after hepatic encephalopathy. The antipyrine clearance measured in 13 patients during hepatic encephalopathy (4.6 ml/min. S.D. 14) was significantly lower than that of 5 patients investigated 4 weeks before or after hepatic encephalopathy (9.6 ml/min. S.D. 1.9). The clearance of antipyrine as a measure of a quantitative liver function is substantiated by the present observations, and its use as a prognostic indicator of acute liver failure is suggested.


The formation of bile acids in patients with portal liver cirrhosis. Bile acid kinetics were characterized in 8 patients with portal liver cirrhosis with the aid of 24-14C-cholic acid and randomly 3H-labelled chenodeozycholic acid. Although not significant on a statistical basis, pool size, synthesis, and fractional turnover of cholic acid in the cirrhotic patients tended to be smaller than in normolipidaemic controls without evidence of liver disease. The most significant findings in the present patients were the subnormal cholic acid: chenodeoxycholic acid ratio of both bile acid pool size and synthesis and the low concentrations of deozycholic acid in duodenal bile specimens. Possible explanations for these findings are discussed.


The uptake of vitamin B12 by the sediment of jejunal contents in patients with the blind-loop syndrome. Following preincubation of intrinsic factor- (IF-) bound 57CoB12 with the jejunal sediments of 6 patients with the blind-loop syndrome, the mean uptake by the sediments of IF-57CoB12 (28.1 percent plus or minus 4.2 percent S,E.M.) was significantly higher than the mean uptake by jejunal sediments from 5 control patients (5.8 per cent plus or minus 3.5 percent) (p smaller than 0.01). The uptake by the sediments significantly decreased when the incubations were carried out in the presence of lincomycin and neomycin. The jejunal sediments from the patients with the blind-loop syndrome inhibited the uptake of IF-57CoB12 by perfused rat intestinal segments (p smaller than 0.01), whereas the sediments from the control patients had no such inhibitory effect (p smaller than 0.5).


Biliary lipids during vitamin C feeding in healthy persons. Inspired by the hypothesis that vitamin C controls the transformation of cholesterol into bile acids, the biliary lipid composition was examined in 10 healthy persons before and after 7 to 15 days' treatment with alrge doses of ascorbic acid. No significant difference between the values before and after treatment were found. It is stressed that the study does not allow evaluation of the hypothesis, but it may be concluded that vitamin C most likely has no place in the medical treatment of cholesterol gallstones.


Lactoferrin in the duodenal juice of patients with chronic calcifying pancreatitis. We have shown the presence of lactoferrin in the pancreatic juice of patients with chronic calcifying pancreatitis (CCP) and its absence in controls. In this work, lactoferrin has been found in saliva, but neither in gastric juice nor in bile. Therefore, a technique for collecting the human duodenal juice with a rubber tube and preventing its contamination with saliva is described. In the duodenal juice of 15 patients with CCP, 52 controls without evident pancreatic diseases, and 9 cases of pancreatic diseases other than CCP, lactoferrin has been searched for by immunological methods before and after an intravenous injection of CCK-PZ (3 U CHR) + secretin ( C U). The lactoferrin test in positive in 5, inconclusive in 6, and negative in 41 cases, and in the 9 cases of non-CCP pancreatic diseases it is negative. The use of this test in the diagnosis of CCP is proposed.


Factors interfering with the comfort of old people in homes for the aged. Some factors influencing the comfort of old people (mean age 73 years) in a modern home for the aged were studied. Most (76 percent) of the old persons were satisfied with their living conditions. Only one-fourth (24 percent) of the inmates were dissatisfied. The most important factors causing dissatisfaction were discomfort due to illnesses, and disagreement with other residents. On the whole, the old people were more satisfied with their life at home for the aged than is ofter supposed.


Varicose ulcers.

Varicose ulcers. The results of a combined dermatological and surgical treatment of varicose ulcers was studied in 100 patients. This chronic disease, often persisting for decades, was halted in 90 percent of leg operated upon. Even when the general outcome of the treatment was favourable, it was found that, for 5 out of the 12 ulcers which were the same or larger in size at follow-up than before operation, the patient assessed the result as good or even excellent. This finding deserves further study. It indicates that patients and physicians sometimes use different standards by which to measure therapeutic success.


Organisational structure and its effect on the therapeutic activity and effectiveness in an american mental health center. The mental health center movement represents a new mode of care for the mentally ill. People are treated on an out-patient basis rather than in institutions. The therapeutic work is mainly carried out by so-called paraprofessionals who seem to be well qualified for the job. However, when organizing such a treatment system there appear to  be several important factors which need to be taken into account: (1) the therapist's need to work individually and independently, (2) the therapist's need for personal training, (3) the therapist's need to be heard when they channel information from the community to the service system, (4) the need for open and direct communication in the system to ensure that the therapists work within the frame of accepted therapeutic procedures, (5) the importance of the therapists' being represented at the highest decision-making level in the system in order to ensure that their needs are met. The author stresses this as an inevitable necessitiy in order to give the therapists the appropriate working-background.


Conviction for drunkenness--a late symptom among female alcoholics. A proband group was selected, consisting of 71 female alcoholics subjected to compulsory treatment by the Temperance Board in Malmö. For the period beginning 20 years before, up to, and including a maximum of 9 years after the first compulsory treatment, less than one conviction was expected, according to a calendar year- and age-specific risk table for Swedish women. During that period, 44 of the probands had been convicted for a total of 219 drunkenness offences. Before then, no offences were recorded. In relation to the expected incidence, the observed was not particularly high at the beginning of the period. From the 11th to the 2nd year before the first compulsory treatment, it increased to an extremely high level, where it remained. The ratio of offences per offender and year was constant during the observation period. The average age at the first offence was high: 35.5 years. Gonorrhoea, recorded criminal offence, and receipt of public assistance appeared much earlier. Drunknness was more common on Fridays and Mondays among the least complicated cases. A more even distribution on week-days seems to be characteristic for the most advanced alcoholics.


Venereal diseases among female alcoholics. The incidence of gonorrhoea among 71 female alcoholics was studied from the twentieth year before, to the ninth year after the first compulsory treatment by the Temperance Board of Malmö. Twenty-five probands had, at some time, had gonorrhoea. The mean age at the first infection was high, over 28 years. None the less, the onset of gonorrhoea was an early "symptom". Recorded criminal offence, receipt of public assistance, and conviction for drunkenness usually appeared later. Each individual's risk of contracting gonorrhoea was assessed from tabulated data concerning the gonorrhoea incidence among Malmö women in general, specified by calendar year and age. A total of 53 infections was observed, as against 6.9 expected. The ratio of observed to expected gonorrhoea was not particularly high in the early period of observation. From the twelfth year before, up to one year before, the first compulsory treatment, the ratio increased to roughly fifteen to one. This high ratio remained during the subsequent years. Syphilis was diagnosed in five probands.


A computer based system for gynecological cytology. A computer system is described for cytological report and registration routines in gynecological practice. The sociomedical advantages of the integration of such a computer system with a previously described computer system for organized pynecological health control are pointed out.


Socio-medical follow-up examination of 1 143 greenlanders surgically treated for pilmonary tuberculosis at Queen Ingrid's Hosptial at Godthåb in the years 1954-1966. A follow-up examination of 1 143 Greenlanders operated on for pulmonary tuberculosis in the years 1954-66 is reported. The main group consists of 785 resected patients. At follow-up 2=12 years after operation all patients were traced. One hundred and four (9 percent) had died; the remaining 1 039 had all been restored to health. Ninety percent of the ex-patients were fully or partially fit and 1 percent unfit for work. Length of observation, time of resumption of work, reasons for change (if any) of occupation, work capacity in relation to the nature of the surgical interventions, and the patients genreal condition as well as housing  situation are discussed. National assistance in Greeland is mentioned in brief.


An evaluation of the official swedish statistics on seriously injured in road traffic accidents. Only 32 per cent of the category "seriously injured" in road traffic accidents were correctly registered as such in the official road traffic accident statistics. Furthermore, 25 percent were registered, though wrongly, as "slightly injured". Consequently almost one-half of the seriously injured were not registered at all, and they constituted a drop-out which contributes a bias to the statistics obtained. False registration is primarily associated with short-term hospitalization and absence of surgical operations during the hospital stay, i.e. slight injuries, and low age. The material analysed was comprised of 2689 individuals from hospital or road traffic accident statistics covering the Uppsala hospital region during 1966.


[Indications and types of synovectomy].

[Indications and types of synovectomy]. Synovectomy is the routine surgical treatment for cases of therapy-resistant exudative synovitis or teno-synovitis, which are frequently seen in cases of rheumatoid arthritis and less frequently in synovial osteochondromatosis, pigmented villo-nodular synovitis and degenerative joint diseases. The best results are obtained following a so-called "early synovectomy", which means a synovectomy performed prior to the onset of destructive changes of bone and cartilage and before the occurrence of irreversible mechanical distension of ligaments and capsules. When carried out under the above mentioned conditions, complete local relief of pain can be achieved in nearly all cases. In rheumatoid arthritis the pain relief may be temporary or permanent depending on the disease progression in each individual case. Statistically, the danger of relapse increases in proportion to the length of time following synovectomy. Analogous results can be obtained by the use of chemical (osmic acid 2%) or radioactive (Er-165, Re-186, P-32, Y-90) synovectomy. Further experience with these agents will be necessary to determine to what degree they can replace surgical therapy.


[Risk factors and age].

[Risk factors and age]. The known risk factors for atherosclerosis do not possess the same significance in young people as in the elderly. Hypercholesterolemia, diabetes and cigarette smoking appear to have a greater bearing below the age of 50 than later, particularly in myocardial infarction but also in apoplexy. On the other hand, hypertension is an important factor in the young and, especially in the case of apoplexy, even more so in advanced age. There is marked difference with regard to preexisting heart disease, which scarcely plays a role in myocardial infarction of the younger patient but is a factor in some 50% of hemiplegia cases. Only one fifth of elderly patients with this disease have no preexisting carcdiopathy. The similarity of the risk factors in elderly patients either with or without apoplexy is due to the fact that arteriosclerosis is already established in both groups and the risk factors which give rise to ischemia, thrombosis or embolism assume prominence. The therapeutic implications are briefly discussed.


Laser raman spectroscopy--new probe of myosin substructure. Laser Raman spectroscopy is used to probe the heterogeneous substructure of the large contractile protein myosin. Some peaks are assigned to specific chemical groups of the molecule; others, notably the conformationally sensitive amide III vibrations, provide information on the structurally distinct regions of the molecule. Deuteration of the NH groups is instrumental in the assignment of these vibrational modes. The relative intensities of bands typical of alpha-helical conformations (near 1265 and 1304 cm-1) and bands associated with nonhelical structure (near 1244 cm-1) are sensitive indicators of myosin substructure and represent potentially useful probes of conformational changes.


Thick and thin filaments in postmitotic, mononucleated myoblasts. Addition of cytochalasin B to primary muscle cultures allows the physical separation of postmitotic myogenic cells from replicating presumptive myoblasts and replicating fibroblasts. Mononucleated, postmitotic myoblasts proceed without fusion to synthesize myosin and actin and to assemble these proteins into thick and thin filaments. Although sarcomeres oriented in tandem are not evident and A, H, and I bands are atypical in these mononucleated myoblasts, the irregularly scattered clusters of myofilaments are assembled into remarkably normal interdigitating arrays. These scattered clusters of stacked thick and thin filaments permit the cell to contact spontaneously in the presence of cytochalasin B.


Retinal degeneration associated with taurine deficiency in the cat. A degeneration of the retinal photoreceptor cells develops in cats when casein is the source of dietary protein. Amino acid profiles indicate that the degeneration is associated with a selective decrease in plasma and retinal taurine concentrations. A sulfur amino acid deficit in the casein diet combined with specific amino acid requirements of the cat appear related to this unique expression of taurine deficiency.


Moving visual phantoms: a new contour completion effect. Moving contours surrounding an empty region make phantoms appear to move through the empty region. The phantoms are contours, dimmer than the inducing contours but of the same pattern, color, speed, and direction of movement. The phantoms originate in the brain and may be related to completion effects most often seen with visual pathology.


Learning: rapid aversive conditioning in the gastropod mollusk Pleurobranchaea. Untrained Pleurobranchaea feed voraciously when presented food and withdraw from electrical shocks. We trained experimental animals in ten trials spaced 1 hour apart to withdraw from food alone by electrically shocking them if they fed or were indifferent to food. The greatest increase in the number of learned withdrawal responses occurred within 12 hours after conditioning, and was accompanied by long-lasting increased in the threshold and latency of feeding responses. Control animals, which received food and shock alternately (unpaired) every half hour, showed considerably weaker changes than experimentals. These control responses quickly returned to initial levels after conditioning.


Ape limb bone from the oligocene of Egypt. An ulna attributed to Aegyptopithecus zeuxis provides the first evidence for interpreting the locomotor behavior of the earliest apes. The fossil indicates that Aegyptopithecus was an arboreal quadruped and that the primitive hominoid locomotor pattern was most nearly analogous, among living primates, to that of Alouatta, the howler monkey.


Horizontal cells in cat retina with independent dendritic systems. Cat horizontal cells are retinal neurons with two functionally distinct parts: the cell body receives signals predominantly from cones, while the terminal arborization receives predominantly from rods. The long thin process connecting these parts neither generates impulses nor allows significant passive electrotonic conduction between them.


Orientation of gull chicks exposed to project Sanguine's electromagnetic field. Birds tested on clear days in the normal geomagnetic field showed a significant clustering of headings about a predicted bearing corresponding with the direction of migration. Individuals tested when a large antenna was energized dispersed randomly. Magnetic fields associated with such conductors may be sufficient to confuse orienting birds.


Sexual behavior: Extreme reduction of postejaculatory refractory period by midbrain lesions in male rats. The refractory period that characteristically follows ejaculation was abolished or significantly reduced by rostral midbrain lesions in male rats. The postejaculatory vocalization was also abolished or reduced, but other aspects of copulatory performance were unaffected. The results were attributed to disruption of biogenic amine pathways that pass from the ventral part of the rostral midbrain into the posterior hypothalamus.


Social modification of alcohol consumption in inbred mice. The strain-specific "preference" for, or "aversion" to, an alcohol solution in a choice situation on the part of C57BL and DBA mice is believed to be under genetic control. But social rearing conditions are now shown to alter the voluntary consumption of alcohol, so that DBA weanling mice housed for 7 weeks with adult C57BL mice increase--and C57BL weanling mice housed with DBA adults decrease--their alcohol intake. Although substantial and highly significant changes in alcohol self-selection occur, strain-specific phenotypes are not reversed.


Tetrodotoxin: Occurrence in atelopid frogs of Costa Rica. The potent neurotoxin tetrodotoxin, which has previously been found in puffer fish of the order Tetraordontiformes, a goby (Gobius criniger), and the California newt (Taricha torosa), has now been identified in the skins of frogs of the genus Atelopus from Costa Rica.


Chlorofluorocarbon sources of environmental contamination. The quantities of chlorofluorocarbons (FCC's) used commercially in the United States and globally are reviewed, and estimates of environmental release from the applications are made. The results indicate that sizable quantities of the FCC's that have been produced have not yet reached the environment and that regulation of U.S. applications would partly reduce, but not end, the possible destruction of stratospheric ozone.


Angiotensin II stimulation of prostaglandin production in cultured human vascular endothelium. Immunoreactive material resembling prostaglandin E accumulates in the medium of cultured human umbilical vein endothelial cells. Prodcution is inhibited by indomethacin and stimulated by angiotensin II. Prostaglandin secretion by endothelium may be important in platelet-dependent thrombotic phenomena, and in local control of vascular permeability and tone in vivo.


Clinical Mammography. A review of the radiologist's role in disease of the breast. Some of the recent trends in the detection of breast lesions, in particular carcinoma, are reviewed. The value, indications, accuracy and limitations of mammography are outlined. Malignant calcifications and their localisation for surgery, specimen radiography, cysts of the breast, duct discharge and the problem of juvenile breast lumps are discussed. The possible hazards from radiation should not be deterrent in any examination with a specific clinical problem. The position may have to be reviewed if extensive use is made of mannography in screening well women.


The radiographic appearance of the rheumatoid hand. The early diagnosis of rheumatoid arthritis ensures a timeous prognosis and appropriate therapy for this chronic disease. The radiograph of the hand is a valuable aid in making this diagnosis, but accurate interpretation is difficult. An outline of the X-ray changes seen in the rheumatoid hand is presented, and the salient points in the differential diagnosis are outlined.


Bladder neck stenosis in the male.

Bladder neck stenosis in the male. Bladder neck stenosis is defined. The symptoms, signs, diagnosis and treatment are discussed. The results of simple transurethral incision of the bladder neck, performed in 60 patients, are recorded.


[Operative surgery of giant bilateral bullae of the lungs]. Three patients with giant bilateral emphysematous bullae are presented. In each case the bullae occupied a third to half of each hemithorax and the remaining lung tissue was compressed. The most informative pre-operative information was gleaned from the standard chest radiograph. All patients underwent simultaneous bilateral resection of the bullae. There was no mortality and the morbidity was limited. Subjectively all patients improved. Median sternotomy was the approach in one patient and we regard this as an effective approach in cases where bilateral bullae have to be removed.


Typhoid perforation of the ileum: A therapeutic dilemma. Thirty-eight cases of typhoid perforation of the terminal ileum were encountered during a three-year period. Fourteen cases were treated conservatively, with a mortality of 36%. During the same period, the surgical mortality improved from 50% in 1972 to 11% in 1974. It is recommended that typhoid perforation be treated by operation.


Nasotracheal intubation in acute laryngotracheobronchitis. The case histories of 150 children admitted to hospital with acute laryngotracheobronchitis (LTB) are reviewed. Relief of severe upper airway obstruction was achieved by nasotracheal intubation in 27 children (18%). There was no mortality in this series. Nasotracheal intubation is therefore a safe and effective means of treating severe LTB. In addition, the importance of meticulous nursing care is stressed.


Pathology of malignant melanoma of the skin in Black Africans. Follow-up data (over a 3-year period) and the histological appearances of primary lesion were studied and related in 40 Black patients with malignant melanoma. This to our knowledge is the first study in Black African patients. It was found that they present with large deeply invasive lesions, particularly on the foot. The prognosis is poor, with an over-all 3-year survival rate of 35%. The histological features used to assess the prognosis of malignant melanoma in Whites, that is histogenetic pattern, size and shape of the lesion, level of invasion, presence of ulceration and mitotic activity would seem to be equally applicable in Black patients. In addition, marked cellular pleomorphism, haemorrhage, necrosis and fibrosis within the tumour are bad signs. In this series lymphocytic infiltration, either within the tumour or at the edge, possibly indicative of an immune response, seemed to be of favourable prognostic import. Surprisingly, a lesion histologica-ly that of lentigo maligna melanoma was found on the feer of some blacks and could be related to much more favourable survival figures.


Control of acute aortic dissection.

Control of acute aortic dissection. An experimental model of acute aortic dissection has been designed in an effort to examine myocardial contractility and systolic arterial pressure as factors influencing the progression of dissection. Thirty mongrel dogs divided into three experimental groups underwent left thoracotomy and construction of a standard intimal tear in the proximal descending aorta. Nine of ten animals in the control group showed progression of the aortic dissection a mean of 81.5 percent of the distance from the aortotomy to the celiac axis. Group II consisted of ten dogs pretreated with propranolol. The myocardial contractility (dp/dt) was significantly depressed in this group without change in systolic pressure. However, progression of dissection occurred in nine of ten animals as in the control group. In Group III, ten dogs were pretreated with trimethaphan lowering the systolic blood pressure to 90 mm. Hg and depressing the dp/dt to levels equal to those of Group II. There was no progression of aortic dissection in any of the animals in this group. The results indicate that, under these experimental conditions, depression of myocardial contractility alone has no inhibitory effect on the progression of dissection. When controlled hypotension is added to myocardial depression, aortic dissection is inhibited completely.


The protective effects of induced hyperkalemia during total circulatory arrest. Three groups of adult mongrel dogs were subjected to 15 minutes of toal circulatory arrest. One group was infused with one liter of Krebs-Hensleit solution and kept normothermic, one group was infused similarly and their body temperature was lowered to 10 to 15 degrees C., and the third group was kept normothermic and infused with hyperkalemic solution. Adenosine triphosphate (ATP) and creatine phosphate levels in the brain during and after the ischemic period were not significantly different in the three groups and glycogen levels tended to remain higher in the hypothermic group. None of the normothermic dogs survived, but all of the hypothermic and hyperkalemic animals survived and were grossly normal. These data indicate that hyperkalemai does offer some protection to the brain during periods of circulatory arrest. It also appears that survival and persistence of brain function do not correlate necessarily with levels of high energy compounds in the brain.


Effect of various corticosteroids upon the phagocytic bactericidal activity of neutrophils. Corticosteroid compounds are used broadly in surgical practice, although mechanisms remain unclarified and efficacy in some situations remains unproved. A recognized adverse effect of steroids in all doses is the potentiation of infection. Specific derivatives of the glucocorticoids appear to have varying degrees of effectiveness in the enhancement of bacterial infection. To evaluate such effects objectively, a series of experiments was undertaken to measure the phagocytic-bactericidal activity of polymorphonuclear leukocytes. This study examines the differential effects of clinical dose equivalents of four glucocorticoid derivatives in depressing in vitro neutrophil phagocytic-bactericidal function. Neutrophils separated from normal human plasma were incubated in vitro in the presence of hydrocortisone sodium phosphate, hydrocortisone sodium succinate, dexamethasone sodium phosphate, and methylprednisolone sodium succinate. Hydrocortisone sodium phosphate, hydrocortisone sodium succinate, and dexamethasone sodium phosphate produce variable, short-term inhibitory effects upon the systems within the neutrophil which are responsible for its bactericidal competency. Methylprednisolone sodium succinate appears to be free of these adverse effects. These in vitro experiments indicate that diminished risk of infection should attend the use of methylprednisolone sodium succinate, although the precise mechanism have not been defined.


Transplantation of the parathyroid glands in man: clinical indications and results. The physiologic function of human parathyroid autografts and allografts has not been demonstrated conclusively. During the past 30 months, we have transplanted parathyroid glands in 29 patients and tested their functional status. One immunosuppressed aparathyroid patient received a parathyroid allograft from a parent who previously had been his renal transplant donor. Twenty-seven patients with renal failure and secondary hyperparathyroidism received parathyroid autografts immediately after total parathyroidectomy, and one patient received a parathyroid autograft at the time of total parathyroidectomy for primary chief cell hyperplasia. At transplantation 1 times 1 mm. parathyroid pieces were grafted into the forearm musculature. Of 11 transplanted patients (one allograft and ten autografts) followed for 1 year, ten are normocalcemic; only two (autografted patients) are on supplemental calcium. Ten of the 29 patients have had biopsies performed, and all have had intact parathyroid architecture and intracellular secretory granules demonstrated by light and electron microscopy. Parathyroid hormone content in the grafted tissue of five patients was 179 plus or minus 118.8 ng. per milligram. In 11 random patients in whom bilateral measurements have been made, the parathyroid hormone content in the antecubital vein blood draining the grafted tissue has been markedly higher than that in the simultaneously sampled antecubital vein blood of the nongrafted arm. These data demonstrate that parathyroid autografts or allografts secret hormone and maintain a normal serum calcium in the host.


The mechanism of myocardial damage following potassium citrate (Melrose) cardioplegia. To determine the reasons for clinical failure of Melrose solution, potassium arrest was studied in isolated working rat hearts. Eight control hearts were stable for 2-1/2 hours. After 1/2 hour of work, 42 experimental hearts were subjected to 1 hour of ischemis by aortic cross-clamping with unmodified ischemia in eight hearts and ischemia with simultaneous intracoronary injection of 5 ml. of 4 degrees C. (1)Krebs-Henseleit buffer in seven hearts (2)potassium chloride buffer in six hearts, (3)potassium citrate buffer in eight hearts (both 26 mEq. per liter of K, approximately 300 mOsm. per liter), (4)Melrose solution in seven hearts (greater than 200 mEq. per liter of K, greater than 400 mOsm. per liter), (5)hypertonic potassium citrate buffer in six hearts (26 mEq. per liter of K, greater than 400 mOsm. per liter). The pH of all solutions was 7.8 plus or minus 0.1. After recovery isotonic potassium citrate- and potassium chloride-arrested hearts and time-matched control hearts showed no significant differences in cardiac output, coronary flow, systolic pressure, or heart rate. Hypertonic potassium citrate decreased the recovery of cardiac function after arrest and Melrose arrest was not significantly different from unmodified ischemia. Intracoronary cold isotonic Krebs-Henseleit buffer was better than Melrose arrest but inferior to 26 mEq. er liter of potassium arrest. Arrest with 26 mEq. per liter of potassium augments perfusion hypothermia and prevents significant functional and histologic myocardial damage during 1 hour of ischemis. Previous authors assumed that hypertonicity and citrate were responsible for poor results with Melrose solution, but high potassium concentration is the major deleterious factor with hypertonicity playing a contributory role.


Reappraisal of timing for exploration of civilian peripheral nerve injuries. Operative as well as electrophysiologic experience with 213 major nerve injuries over the last 8 years and primate experiments form the basis of this reappraisal. Those lesions in continuity resected (58 of 172) usually had no response to stimulation or nerve action potential (NAP) at 8 weeks or longer after injury but were not necessarily complete lesions on clinical examination or electromyography. Axonal organization and maturity were of such poor quality that functional regeneration would not have resulted. Despite preoperative evidence of an incomplete lesion, operative studies confirmed a complete lesion in 21 instances. In 103 lesions NAP's could be recorded and, where neurolysis was done, recovery was acceptable in 91 percent. Many of these lesions had appeared complete on preoperative evaluation. Nerves transected by glass and repaired primarily had superior electrical and functional recovery to those repaired secondarily, although variations in clinical settings prevented statistical analysis. Experimental work in 20 primates with glass-wounded nerves favored primary repair, for NAP, evoked muscle action potential, and strain gauge studies of muscle power were superior in 14. Lesions in continuity should have exploration delayed until 8 weeks so that physiologic decisions regarding need for resection and repair can be made. Transecting injuries should be explored primarily, those without contusinve element repaired immediately, and those with contusion repaired 3 weeks after injury.


Effect of bacillus Calmette-Guerin immunotherapy on tumor antigen-induced lymphocyte-stimulated protein synthesis in melanoma patients. Changes in in vitro lymphocyte-stimulation protein synthesis (SPS) of 40 melanoma patients following incubation with 3M KCl extracts of allogenic melanoma, lung carcinoma, and sarcoma antigens and phytohemagglutinin (PHA) were quantitated by measuring H-3-leucine uptake. One of eleven "untreated" melanoma patients stimulated significantly to the melanoma antigen. However, this lymphocyte response was not significantly different from that of the normal subjects. Patients who received systemic bacillus Calmette-Guerin (BCG) by the tine technique for 3 months and for 6 months had significant increase in lymphocyte protein synthesis following incubation with melanoma antigen. There were no significant differences in PHA responses between the "untreated" melanoma patients and the BCG-treated group. Testing of serial lymphocyte samples from nine melanoma patients before treatment and at monthly intervals thereafter confirmed these observations. Furthermore, no change in serial complement-fixing antibody titers to melanoma antigen was noted in the BCG-treated patients. These results demonstrated that in vitro lymphocyte responses to melanoma antigen may be augmented by BCG therapy.


Capillary muscle blood flow in human sepsis. Tissue perfusion was determined by cardiac index (Cl) and skeletal muscle capillary blood flow (MBF), and arteriovenous oxygen difference (AVD) and oxygen uptake were compared in seven patients with severe spesis and eight nonseptic patients. Skeletal capillary muscle blood flow also was measured before and after a 2 day fast in 14 normal volunteers. In both septic and nonseptic patients, MBF varied directly with Cl. The average muscle blood flow was greater in septic than in nonseptic patients and, in addition, was greater per unit Cl. AVD in septic patients was narrower than in nonseptic patients. Septic patients with an AVD of less than 4 ml. of O2 had markedly higher MBF and Cl than did septic patients with an AVD greater than 4 ml. of O2. Fasting normal volunteers who, like the septic patients, would be catabolic had a significant increase in MBF during the fast. Although peripheral shunts are not ruled out ans an explanation of the hyperdynamic circulation in sepsis, the evidence is against their existence, at least in skeletal muscle, since capillary flow increases in direct proportion to cardiac output. If capillary flow is increased in fact in sepsis, then flow like blood pressure becomes less of a critical factor in explaining the demise of the septic patient. It might be postulated that the increased capillary flow seen in sepsis is secondary to the mobilization of amino acids from the body cell mass for gluconeogenesis and energy.


Hemorrhagic infarction: A reperfusion injury following prolonged myocardial ischemic anoxia. Sixteen canine myocardial pedicle preparations were divided into four groups. Group I received 60 minutes of reversible ischemic anoxia, Group II 90 minutes, Group III 120 minutes, and Group IV 180 minutes. Transmural ischemic infarction was present in Group I. With longer periods of anoxia, capillary disruption occurred, first in the subendocardium (90 minutes) and then transmurally (180 minutes). Reperfusion after ischemic, anoxic time periods of 90 minutes or greater produced hemorrhagic necrosis, the extent of which was directly proportional to the duration of the preceding ischemic, anoxic period. One hundred and twenty patients with aortic valve replacement surgery then were analyzed retrospectively. Of the 25 deaths, seven were due to immediate postinfarction, five from subendocardial hemorrhagic necrosis. The common factor in the patients with hemorrhagic infarction was a markedly reduced coronary flow (45 to 55 ml. per minute) for more than 70 minutes during the interval of cardiopulmonary bypass. Although other factors may be involved, it is hypothesized that the main cause is a degree of localized ischemia of sufficient duration to induce capillary disruption and subsequent postbypass hemorrhagic necrosis when normal coronary artery perfusion is resumed.


Prenatal effects of the cancer chemotherapeutic drug ICRF 159 in mice, rats, and rabbits. The antimitotic, anticancer drug ICRF 159 [(plus or minus)-1,2,'bis(3,5'dioxopiperazine-l-yl)propane] when given to pregnant BALB/c mice, Sprague-Dawley and Wistar rats, and New Zealand white rabbits had mainly embryolethal effects; the margin between no apparent activity and total embryolethality was narrow. A small percentage of fetuses were malformed and some exhibited retarded development. In all three species the time of maximum sensitivity to the drug was early in gestation, between days 6-10 in mice, 6-8 in rats, and 7-10 in rabbits.


Teratogenesis of acetazolamide in the CBA/J and SWV strains of mice. I. Teratology. SWV mice were totally resistant to the teratogenic and embryolethal actions of acetazolamide. The time of maximal sensitivity to acetazolamide-induced ectrodactyly in the CBA/J strain was the middle of day 10; the dose response at this time was studied. Comparison of the responses of the two strains and reciprocal hybrids indicated that sensitivity is a property of the embryo and is not maternally mediated. SWV mice were also resistant to dichlorphenamide which suggests they may be resistant to many or even all teratogenic carbonic anhydrase inhibitors.